These studies aim to define the importance of blood coagulation, fibrinolysis, complement and presently known kinin-forming enzymes in plasma in maintaining the integrity of the vasculature. Vascular function can be altered by certain polypeptides, exemplified by increased vascular permeability characteristic of hereditary angioneurotic edema (HANE). Definition of the chemical nature of vasoactive polypeptide extractable from HANE plasma should permit estimation of the importance of such a mediator in pathophysiologic changes in normals through use of an antibody to the peptide. Serum inhibitor of C 1 esterase displays marked heterogeneity of non-functional allotypes in HANE. Since it regulates plasma enzymes active in coagulation, fibrinolysis and kinin release, characterization of its unusual inherited deficiency in HANE by immunologic procedures might define unidentified inhibitor-like protein in HANE sera, deficient by other criteria, but inhibitory to hemostasis or kinin release. In determining mechanisms of indirect activation of the first component of complement in HANE plasma by activated Hageman factor, added insights into relationships between clotting and complement action should be gained. Plasmin may be involved, and variability of its hydrolytic actions will be evaluated by examining some products of proteolysis by plasmin preparations.